ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare but increasingly recognized syndromes characterized by chronic muscle inflammation of unknown cause. The finding of other autoimmune diseases in association with IIM, the inflammatory pathology, the response to immunosuppressive therapy, and the frequent occurrence of autoantibodies all support the notion that the IIMs are autoimmune diseases. IIM patients are unique in their immune targeting of a group of autoantigens involved in protein synthesis. Recent studies of the autoantibodies that bind these autoantigens (the myositis-specific autoantibodies) suggest that they arise by mechanisms that closely resemble standard immune responses. There is increasing interest in and efforts directed toward dividing the rheumatic diseases into more uniform groups for purposes of better defining etiology and pathogenesis. This approach has been useful in the analysis of the IIMs in which new approaches, subsetting patients by autoantibodies, have produced more homogeneous groupings. Recent data on predisposing immunogenetic factors in different clinical and serologic subsets of IIM patients also suggest that these disorders result from environmental agents acting on groups of genetically restricted individuals to induce immunologic activation and subsequent tissue pathology. This review summarizes these findings about the origins of the myositis-specific autoantibodies and their epidemiologic, clinical, prognostic, and immunogenetic associations.

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Although the etiologic stimulus has not been identified, there is considerable evidence that cell-mediated immune mechanisms play an important role in the pathogenesis of polymyositis-dermatomyositis: 1) a discrete chronic mononuclear cell infiltrate is almost always present in the affected muscles of patients with polymyositis-dermatomyositis; 2) the predominant cell of this chronic mononuclear cell infiltrate is the T lymphocyte; 3) the infiltrating T cells appear to be activated because they express activation antigens, such as major histocompatibility complex class II molecules; 4) peripheral blood lymphocytes express activation markers, they are sensitized to muscle, and they seem to be cytotoxic to musclein vitro; and 5) pathologic similarities reminiscent of polymyositis are found in animal models of experimental myositis. Recent observations on cell-mediated immunity in polymyositis-dermatomyositis, discussed in this review, provide new insights into the pathogenesis of the inflammatory myopathies.

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The mainstay of therapy for polymyositis-dermatomyositis continues to be corticosteroids either alone or in combination with other immunosuppressive agents. Intravenous cyclophosphamide may be beneficial in some patients, and success with cyclosporine has been reported in children with dermatomyositis. Intravenous gamma-globulin has resulted in short-term benefit for both children and adults. Other seldom-used therapies for the refractory patient with myositis include plasmapheresis, total body irradiation, and thymectomy.

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The termmetabolic myopathyrefers to a heterogeneous group of conditions that have in common abnormalities of muscle energy metabolism that result in skeletal muscle dysfunction. Most recognized metabolic myopathies are considered primary, represent inborn errors of metabolism, and are associated with known or postulated defects that affect the ability of muscle fibers to maintain adequate ATP concentrations. Traditionally, these diseases are grouped into abnormalities of glycogen, lipid, purine, and mitochondrial biochemistry. This discussion reviews the basic metabolic pathways that regulate normal muscle function; recent observations involving glycogen storage diseases, carnitine deficiency states, and myoadenylate deaminase deficiencies; and lastly, newer techniques available to assess patients with myopathic disorders.

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Animal models have proven very useful in furthering insight into a number of muscle diseases. Studies of ethanol-fed rats are being used to understand the pathogenetic mechanisms underlying acute and chronic myopathy induced by ethanol. Several animal species, including mice, dogs, and cats, develop X-linked muscular dystrophies, which have genetic defects identical to those of Duchenne muscular dystrophy. As in the human disease, these animals lack dystrophin. They are being used to investigate the mechanisms by which lack of dystrophin results in weakness and to examine myoblast transfer as a treatment modality. A model of eosinophilia-myalgia syndrome has recently been induced in Lewis rats by the feeding of L-tryptophan samples that were implicated in the clinical syndrome in humans, making possible studies of the pathogenesis of this interesting new entity. A dermatomyositis-like syndrome occurs spontaneously in dogs, and polymyositis-like illnesses can be induced in mice by immunization with muscle or following infection with selected viruses, especially enteroviruses. Study of the latter is helping us understand mechanisms in the etiology and pathogenesis of inflammatory myositis and virus-induced autoimmunity.

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This review discusses possible markers of scleroderma, including fibronectin gene mutations, major histocompatibility complex class II antigens, anti-Scl-70, and the Fc receptor. The association between genetic and environmental factors is also reviewed, as is a mouse model of human disease.

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Evidence continues to accumulate supportingin vivoactivation of T cells in scleroderma. The studies reviewed reported finding circulating cytokines in scleroderma serum or soluble T-cell membrane molecules, especially soluble interleukin-2 receptor and CDS. The antigens to which T-cell reactivity is directed, if indeed such antigens exist, remain to be identified. Specific humoral immune responses in the form of autoantibodies to nuclear-associated antigens appear to be polyclonal and antigen driven. Although autoantibodies cannot as yet be implicated in disease pathogenesis, patterns of autoantibodies are associated with, but do not reliably define, disease subsets. In patients with Raynaud's phenomenon alone, the absence of autoantibodies is predictive of not developing systemic connective tissue disease, while the presence of autoantibodies indicates an increased risk.

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Fibroblasts within the skin of scleroderma patients constitute a phenotypically heterogeneous population with regard to expression of collagens, cytokines, and cytokine receptors. By in situ hybridization techniques, scleroderma skin is shown to contain a subpopulation of fibroblasts that are stimulated for expression of type VI collagen; the size of this subpopulation is larger than that found in normal skin. The heterogeneity in collagen production among scleroderma fibroblasts can also be demonstratedin vitrofollowing sorting by flow cytometric analysis. An isoform of a cytokine known to be a potent modulator of collagen expression, transforming growth factor-β2, is overexpressed in and around inflammatory infiltrates in biopsies of skin from scleroderma patients. Scleroderma fibroblasts grown in culture express slightly elevated levels of transcripts for transforming growth factor-β1, demonstrated by Northern analysis. Osteonectin, or SPARC (secreted protein, acidic and rich in cysteine), messenger RNA is also clearly elevated in fibroblasts cultured from the affected skin of scleroderma patients. The affinity of epidermal growth factor receptors on fibroblasts derived from the skin of scleroderma patients is decreased compared with that of receptors on normal fibroblasts. Platelet-derived growth factor-β receptors were detectable by immunohistochemical staining in dermal vessels and surrounding fibroblasts in 13 of 14 biopsies of skin of scleroderma patients, whereas they were absent in sections of normal skin. These studies completed within the past year allow recognition of the importance of interactions between cell types, and the possible consequences of alterations in cytokine secretory patterns and cell responsiveness.

ISSN:1040-8711    

出版商:OVID    

年代:1991

数据来源: OVID